The effect of CR 1409, a potent CCK receptor antagonist, on basal and stimulated pancreatic secretion in rat.
The effect of a specific cholecystokinin (CCK) receptor blocker from Rotta Research Laboratorium (Monza/Milano, Italy), CR 1409 (Lorglumide), on pancreatic secretion was investigated. CR 1409 caused a rightward and parallel shift in the dose-response curve of CCK-8-stimulated pancreatic protein secretion in anesthetized rats, demonstrating a competitive mechanism of inhibition. The mean pA2 value, showing the 50% inhibitory dose of CR 1409, was 6.4. CR 1409 proved to be about 1,000 times more potent as a CCK receptor blocker than proglumide, the first glutaramic acid analogue with anti-CCK potential. In conscious rats, pancreatic protein and water secretion were significantly diminished for about 2 h in response to 300 micrograms/kg of CR 1409 given subcutaneously during diversion of pancreatic juice, demonstrating inhibition of endogenous CCK by this new glutaramic acid derivative. By contrast, during reintroduction of precollected pancreatic juice into the duodenum, when the release of CCK is almost totally eliminated, pancreatic secretion was not modified by the same dose.
Takács
T
T
First Department of Medicine, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Nagy
I
I
Pap
A
A
Varró
V
V
D000818:Animals; D001639:Bicarbonates; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000031:analogs & derivatives*; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D012636:Secretory Rate / Q000187:drug effects; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001639:Bicarbonates; D011949:Receptors, Cholecystokinin; D005973:Glutamine; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide